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1. Thermoformed Parylene‐C Cuff Electrodes for Small Nerve Interfacing

Author

Francisco Zurita, Sebastian Freko, Lukas Hiendlmeier, Fulvia Del Duca, Tanja Groll, Olga Seelbach, Katja Steiger, and Bernhard Wolfrum

Subjects
cuff electrodes, locust implantation, parylene-C, peripheral nerve interface, thermoforming process, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
Abstract

Peripheral nerve interfacing plays a crucial role in various healthcare applications. Generally, interfacing peripheral nerves results in a compromise between selectivity and invasiveness. In particular, large nerves carry many axonal fibers, which are difficult to address selectively without penetrating the nerve. Higher selectivity without nerve penetration can be achieved by targeting small nerves with extraneural cuff electrodes. However, in practice, small nerves are challenging to interface appropriately. Herein, a new multielectrode device is presented that can selectively interface small nerves (

Published
2024
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2. Filtration-processed biomass nanofiber electrodes for flexible bioelectronics

Author

Daiki Ando, Tetsuhiko F. Teshima, Francisco Zurita, Hu Peng, Kota Ogura, Kenji Kondo, Lennart Weiß, Ayumi Hirano-Iwata, Markus Becherer, Joe Alexander, and Bernhard Wolfrum

Subjects
Bioelectronics, Biopolymers, High-aspect-ratio materials, Membrane filtration, Implantable Electrodes, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
Abstract

Abstract An increasing demand for bioelectronics that interface with living systems has driven the development of materials to resolve mismatches between electronic devices and biological tissues. So far, a variety of different polymers have been used as substrates for bioelectronics. Especially, biopolymers have been investigated as next-generation materials for bioelectronics because they possess interesting characteristics such as high biocompatibility, biodegradability, and sustainability. However, their range of applications has been restricted due to the limited compatibility of classical fabrication methods with such biopolymers. Here, we introduce a fabrication process for thin and large-area films of chitosan nanofibers (CSNFs) integrated with conductive materials. To this end, we pattern carbon nanotubes (CNTs), silver nanowires, and poly (3,4-ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT:PSS) by a facile filtration process that uses polyimide masks fabricated via laser ablation. This method yields feedlines of conductive material on nanofiber paper and demonstrates compatibility with conjugated and high-aspect-ratio materials. Furthermore, we fabricate a CNT neural interface electrode by taking advantage of this fabrication process and demonstrate peripheral nerve stimulation to the rapid extensor nerve of a live locust. The presented method might pave the way for future bioelectronic devices based on biopolymer nanofibers.

Published
2022
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3. Origami‐Enabled Stretchable Electrodes Based on Parylene Deposition and 3D Printing

Author

Fulvia Del Duca, Lukas Hiendlmeier, Reem Al Fata, George Al Boustani, Inola Kopic, Hu Peng, Beatrice De Chiara, Marta Nikić, Francisco Zurita, Tetsuhiko Teshima, and Bernhard Wolfrum

Subjects
3D printing, microfabrication, origami, parylene, stretchable electronics, Electric apparatus and materials. Electric circuits. Electric networks, TK452-454.4, Physics, QC1-999
Abstract

Abstract Thin film electronic devices based on flexible biocompatible substrates are desired in various fields such as implants, soft robotics, and wearables, where stretchability is often necessary. Structure‐enabled stretchability in flexible thin films can be achieved by introducing origami‐inspired folds, thereby storing excess material in the out‐of‐plane direction to unfold upon stress. When using vapor‐deposited substrates such as parylene‐C, folds can be introduced prefabrication using molds patterned in repeated grooves and ridges. Here, this work reports the fabrication and parametrization of 10‐µm‐thick stretchable origami parylene‐C electrodes using 3D printed molds. The molds are printed with a sinusoidal pattern and tunable amplitude and slope, with accurate printing results up to 60° steepness. A 160‐nm‐thick gold layer on top of the folded parylene is patterned via laser ablation following the 3D mold shape. Depending on the design parameters, the resulting electrodes maintain functionality until 40%–100% strain. By 3D printing the molds, this technique can fabricate electrodes with complete control of the designed directions of stretchability in a rapid prototyping approach.

Published
2023
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4. In vivo closed-loop control of a locust’s leg using nerve stimulation

Author

Francisco Zurita, Fulvia Del Duca, Tetsuhiko Teshima, Lukas Hiendlmeier, Michael Gebhardt, Harald Luksch, and Bernhard Wolfrum

Subjects
Medicine, Science
Abstract

Abstract Activity of an innervated tissue can be modulated based on an acquired biomarker through feedback loops. How to convert this biomarker into a meaningful stimulation pattern is still a topic of intensive research. In this article, we present a simple closed-loop mechanism to control the mean angle of a locust’s leg in real time by modulating the frequency of the stimulation on its extensor motor nerve. The nerve is interfaced with a custom-designed cuff electrode and the feedback loop is implemented online with a proportional control algorithm, which runs solely on a microcontroller without the need of an external computer. The results show that the system can be controlled with a single-input, single-output feedback loop. The model described in this article can serve as a primer for young researchers to learn about neural control in biological systems before applying these concepts in advanced systems. We expect that the approach can be advanced to achieve control over more complex movements by increasing the number of recorded biomarkers and selective stimulation units.

Published
2022
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5. Soft peripheral nerve interface made from carbon nanotubes embedded in silicone

Author

Korkut Terkan, Francisco Zurita, Touba Jamal Khalaf, Philipp Rinklin, Tetsuhiko Teshima, Tobias Kohl, and Bernhard Wolfrum

Subjects
Biotechnology, TP248.13-248.65, Physics, QC1-999
Abstract

Electrodes for interfacing implantable electronics and neural tissue are of great importance to gain a better understanding of the nervous system and to help people suffering from impaired body functions due to nerve lesions or lost organ functionality. In particular, neurostimulation techniques for bioelectronic medicine rely on the development of mechanically and electrochemically stable electrodes. While contemporary electrodes are based mainly on metals, new materials are being designed to enhance the mechanical and electrochemical properties of the interface. In this work, a nerve interface based on carbon nanotubes (CNTs) embedded in polydimethylsiloxane (PDMS) is fabricated and investigated. The fabrication process relies on the selective vacuum filtration of CNT suspensions through a printed wax pattern. The mechanical and electrochemical stability of the nerve interface was validated by 10 000 stretching cycles up to 20% strain and >4 × 106 biphasic stimulation pulses with 32 μC cm−2 per phase. The feedline resistance and electrode impedance showed only minor alterations after the stress tests. The functionality of the nerve interface was demonstrated by successful stimulation of the central nerve cord of a horse leech applying stimulation conditions within the water window of the CNT/PDMS electrodes. This work shows the practical usability of CNT/PDMS composites as electrodes and feedlines in peripheral nerve interfaces for future neuroprosthetic devices.

Published
2020
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6. Establishment of a human iPSC line, IISHDOi004-A, from a patient with Usher syndrome associated with the mutation c.2276G>T; p.Cys759Phe in the USH2A gene

Author

Francisco Zurita-Díaz, María del Carmen Ortuño-Costela, Ana Moreno-Izquierdo, Liliana Galbis, José María Millán, Carmen Ayuso, Rafael Garesse, and M. Esther Gallardo

Subjects
Biology (General), QH301-705.5
Abstract

A human iPSC line, IISHDOi004-A, from fibroblasts obtained from a patient with Usher syndrome, harboring a homozygous mutation in the USH2A gene (c.2276G>T; p.Cys759Phe) has been generated. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus.

Published
2018
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7. Establishment of a human DOA 'plus' iPSC line, IISHDOi003-A, with the mutation in the OPA1 gene: c.1635C>A; p.Ser545Arg

Author

Francisco Zurita-Díaz, Teresa Galera-Monge, Ana Moreno-Izquierdo, Marta Corton, Carmen Ayuso, Rafael Garesse, and M. Esther Gallardo

Subjects
Biology (General), QH301-705.5
Abstract

We have generated a human iPSC line IISHDOi003-A from fibroblasts of a patient with a dominant optic atrophy ‘plus’ phenotype, harbouring a heterozygous mutation, c.1635C>A; p.Ser545Arg, in the OPA1 gene. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus.

Published
2017
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8. Establishment of a human iPSC line (IISHDOi001-A) from a patient with McArdle disease

Author

María del Carmen Ortuño-Costela, Nathalie Rodríguez-Mancera, Marta García-López, Francisco Zurita-Díaz, Ana Moreno-Izquierdo, Alejandro Lucía, Miguel Ángel Martín, Rafael Garesse, and M. Esther Gallardo

Subjects
Biology (General), QH301-705.5
Abstract

Human iPSC line IISHDOi001-A was generated from fibroblasts of a patient with McArdle disease harbouring the mutation, c.148C>T; p.Arg50Ter, in the PYGM gene. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus.

Published
2017
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9. Generation of a human iPSC line from a patient with an optic atrophy ‘plus’ phenotype due to a mutation in the OPA1 gene

Author

Teresa Galera-Monge, Francisco Zurita-Díaz, Ana Moreno-Izquierdo, Mario F. Fraga, Agustin F. Fernández, C. Ayuso, Rafael Garesse, and M. Esther Gallardo

Subjects
Biology (General), QH301-705.5
Abstract

Human iPSC line Oex2054SV.4 was generated from fibroblasts of a patient with an optic atrophy ‘plus’ phenotype associated with a heterozygous mutation in the OPA1 gene. Reprogramming factors OCT3/4, SOX2, CMYC and KLF4 were delivered using a non-integrative methodology that involves the use of Sendai virus.

Published
2016
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10. Generation of a human iPSC line from a patient with Leigh syndrome caused by a mutation in the MT-ATP6 gene

Author

Teresa Galera-Monge, Francisco Zurita-Díaz, Cristina González-Páramos, Ana Moreno-Izquierdo, Mario F. Fraga, Agustin F. Fernández, Rafael Garesse, and M. Esther Gallardo

Subjects
Biology (General), QH301-705.5
Abstract

Human iPSC line L749.1 was generated from fibroblasts of a patient with Leigh syndrome associated with a heteroplasmic mutation in the MT-ATP6 gene. Reprogramming factors OCT4, SOX2, CMYC and KLF4 were delivered using retroviruses.

Published
2016
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12. Fully 3D‐Printed Cuff Electrode for Small Nerve Interfacing

Author

Francisco Zurita, Leroy Grob, Amelie Erben, Fulvia Del Duca, Hauke Clausen‐Schaumann, Stefanie Sudhop, Oliver Hayden, and Bernhard Wolfrum

Subjects
Mechanics of Materials, General Materials Science, Industrial and Manufacturing Engineering, ddc, Research Article, Research Articles, 3D printing, implantable electrode, nerve cuff
Published
2022
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14. 3D Printing of Implants Composed of Nanjing Tamasudare‐Inspired Flexible Shape Transformers

Author

Francisco Zurita, Bernhard Wolfrum, Leroy Grob, Philipp Rinklin, Sabine Zips, Tetsuhiko Teshima, Korkut Terkan, and Lukas Hiendlmeier

Subjects
Materials science, Mechanics of Materials, law, business.industry, Mechanical engineering, 3D printing, General Materials Science, Shape transformation, Transformer, business, Industrial and Manufacturing Engineering, law.invention, ddc
Published
2020

15. Establishment of a human iPSC line (IISHDOi001-A) from a patient with McArdle disease

Author

Alejandro Lucia, María del Carmen Ortuño-Costela, Miguel A. Martín, Marta García-López, Rafael Garesse, M. Esther Gallardo, Ana Moreno-Izquierdo, Nathalie Rodríguez-Mancera, Francisco Zurita-Díaz, Instituto de Salud Carlos III, Comunidad de Madrid, Ministerio de Educación, Cultura y Deporte (España), and European Commission

Subjects
0301 basic medicine, MCARDLE DISEASE, viruses, Induced Pluripotent Stem Cells, Cell Culture Techniques, Genética humana, Cell Line, Kruppel-Like Factor 4, 03 medical and health sciences, stomatognathic system, SOX2, Humans, lcsh:QH301-705.5, Gene, Metabolismo, Genetics, biology, Reproducibility of Results, Cell Biology, General Medicine, biology.organism_classification, Virology, Sendai virus, 030104 developmental biology, lcsh:Biology (General), KLF4, Mutation, embryonic structures, Mutation (genetic algorithm), Glycogen Storage Disease Type V, Female, Ipsc line, Reprogramming, Developmental Biology
Abstract

Human iPSC line IISHDOi001-A was generated from fibroblasts of a patient with McArdle disease harbouring the mutation, c.148C > T; p.Arg50Ter, in the PYGM gene. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus., This work was supported by grants from: 1) the “Fondo de Investigación Sanitaria, Instituto de Salud Carlos III”: PI10/0703, PI13/00556 and PI16/00789 to RG and PI15/00484 to MEG cofunded by FEDER, 2) from the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER): grants 13-717/132.05 and ER16P3AC717 to RG and 3) “Comunidad Autónoma de Madrid” (grant number S2010/BMD-2402 to RG). MDCOC receives grant support from CIBERER and FZD from the Ministerio de Educación, Cultura y Deporte (FPU13/00544). MEG is supported by a “Miguel Servet contract” (CP16/00046) from ISCIII-MINECO-Spain/FEDER-EU.

Published
2017
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16. The mutation m.13513G>A impairs cardiac function, favoring a neuroectoderm commitment, in a mutant-load dependent way

Author

María Esther Gallardo, Francisco Zurita-Díaz, Rafael Garesse, Teresa Galera-Monge, Instituto de Salud Carlos III, European Commission, and Centro de Investigación Biomédica en Red Enfermedades Raras (España)

Subjects
0301 basic medicine, Cardiac function curve, Mitochondrial DNA, Epithelial-Mesenchymal Transition, Mitochondrial Diseases, iPSc, Heart Diseases, Physiology, Mitochondrial disease, Clinical Biochemistry, Mutant, Induced Pluripotent Stem Cells, Embryonic Development, Biology, Bioinformatics, Heteroplasmy, DNA, Mitochondrial, Electron Transport, Mitochondrial Proteins, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Myocytes, Cardiac, Induced pluripotent stem cell, Cardiomyocytes, Neural Plate, Electron Transport Complex I, Transition (genetics), Neuroectoderm, Cell Differentiation, Cell Biology, medicine.disease, Leigh syndrome, Mitochondria, 030104 developmental biology, Phenotype, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Mutation, Leigh Disease
Abstract

Mitochondrial disorders (MDs) arise as a result of a respiratory chain dysfunction. While some MDs can affect a single organ, many involve several organs, the brain being the most affected, followed by heart and/or muscle. Many of these diseases are associated with heteroplasmic mutations in the mitochondrial DNA (mtDNA). The proportion of mutated mtDNA must exceed a critical threshold to produce disease. Therefore, understanding how embryonic development determines the heteroplasmy level in each tissue could explain the organ susceptibility and the clinical heterogeneity observed in these patients. In this report, the dynamics of heteroplasmy and the influence in cardiac commitment of the mutational load of the m.13513G>A mutation has been analyzed. This mutation has been reported as a frequent cause of Leigh syndrome (LS) and is commonly associated with cardiac problems. In this report, induced pluripotent stem cell (iPSc) technology has been used to delve into the molecular mechanisms underlying cardiac disease in LS. When mutation m.13513G>A is above a threshold, iPSc‐derived cardiomyocytes (iPSc‐CMs) could not be obtained due to an inefficient epithelial‐mesenchymal transition. Surprisingly, these cells are redirected toward neuroectodermal lineages that would give rise to the brain. However, when mutation is below that threshold, dysfunctional CM are generated in a mutant‐load dependent way. We suggest that distribution of the m.13513G>A mutation during cardiac differentiation is not at random. We propose a possible explanation of why neuropathology is a frequent feature of MD, but cardiac involvement is not always present., The authors are very grateful to Dr. Munell for kindly providing them the patient's fibroblasts. Contract grant sponsor: Instituto de Salud Carlos III (Fondo de Investigación Sanitaria and Regional Development Fund [ERDF/FEDER]); contract grant numbers: PI10/00703, PI13/00556, and PI16/00489 to R. G. and PI15/00484 and PI18/00151 to M. E. G. Contract grant sponsor: Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER); contract grant numbers: (13–717/132.05 and ER16P3AC717 to R. G.). Contract grant sponsor: Miguel Servet Program from ISCIII; contract grant number: CP16/00046 to M. E. G.

Published
2019

17. Generation of a human control iPSC line with a European mitochondrial haplogroup U background

Author

Francisco Zurita, Cristina González-Páramos, M. Esther Gallardo, Ana Moreno-Izquierdo, Teresa Galera, Rafael Garesse, Agustín F. Fernández, Mario F. Fraga, UAM. Departamento de Bioquímica, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), Universidad Autónoma de Madrid, Comunidad de Madrid, Ministerio de Educación, Cultura y Deporte (España), European Commission, and Instituto de Salud Carlos III

Subjects
0301 basic medicine, Medicina, Cellular differentiation, Cell Culture Techniques, Mitochondrion, Cell Line, Kruppel-Like Factor 4, 03 medical and health sciences, stomatognathic system, Humans, Induced pluripotent stem cell, Medicine(all), Genetics, iPSC, biology, Haplotype, Cell Differentiation, Cell Biology, General Medicine, IPS cells, biology.organism_classification, DNA Fingerprinting, Sendai virus, Mitochondria, Europe, iPS cells, Induced pluripotent stem cells, 030104 developmental biology, Haplotypes, IPSC, POLG, KLF4, Karyotyping, embryonic structures, Defects of intergenomic communication, Reprogramming, Developmental Biology, Human mitochondrial DNA haplogroup
Abstract

Human iPSC line N44SV.5 was generated from primary normal human dermal fibroblasts belonging to the European mitochondrial haplogroup U. For this purpose, reprogramming factors Oct3/4, Sox2, Klf4, and cMyc were delivered using a non-integrative methodology that involves the use of Sendai virus., This work was supported by grants from the “Centro de Investigación Biomédica en Red en enfermedades raras” (CIBERER) (grant 13-717/132.05 to RG), the “Instituto de Salud Carlos III” [Fondo de Investigación Sanitaria and Regional Development Fund (ERDF/FEDER) funds PI10/0703 and PI13/00556 to RG and PI15/00484 to MEG], “Comunidad Autónoma de Madrid” (grant number S2010/BMD-2402 to R.G); T.G. receives grant support from the Universidad Autónoma de Madrid, FPI-UAM and F.Z.D. from the Ministerio de Educación, Cultura y Deporte, grant number FPU13/00544. M.E.G. is staff scientist at the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER).

Published
2016
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18. Advanced therapy medicinal products: Gene therapy

Author

Francisco Zurita, Antonio Ayala, Sandro Argüelles, Mercedes Cano, and Mario F. Muñoz

Subjects
business.industry, Health Policy, Genetic enhancement, Medicine, Bioinformatics, business, Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Published
2015
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19. Generation of a human iPSC line from a patient with Leigh syndrome caused by a mutation in the MT-ATP6 gene

Author

Rafael Garesse, Mario F. Fraga, Cristina González-Páramos, Agustín F. Fernández, Ana Moreno-Izquierdo, Francisco Zurita-Díaz, M. Esther Gallardo, Teresa Galera-Monge, UAM. Departamento de Bioquímica, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), Universidad Autónoma de Madrid, Instituto de Salud Carlos III, European Commission, Centro de Investigación Biomédica en Red Enfermedades Raras (España), and Comunidad de Madrid

Subjects
0301 basic medicine, Medicina, Induced Pluripotent Stem Cells, Cell Culture Techniques, Biology, Cell Line, Human iPSC line, 03 medical and health sciences, stomatognathic system, SOX2, medicine, Humans, Leigh disease, Induced pluripotent stem cell, MT-ATP6 gene, lcsh:QH301-705.5, Gene, Medicine(all), Genetics, fungi, Cell Biology, General Medicine, Mitochondrial Proton-Translocating ATPases, Cellular Reprogramming, medicine.disease, Leigh syndrome, Heteroplasmy, 030104 developmental biology, lcsh:Biology (General), KLF4, embryonic structures, Mutation (genetic algorithm), Mutation, sense organs, Leigh Disease, biological phenomena, cell phenomena, and immunity, Reprogramming, Developmental Biology
Abstract

Human iPSC line L749.1 was generated from fibroblasts of a patient with Leigh syndrome associated with a heteroplasmic mutation in the MT-ATP6 gene. Reprogramming factors OCT4, SOX2, CMYC and KLF4 were delivered using retroviruses., This work was supported by grants from the “Centro de Investigación Biomédica en Red en enfermedades raras” (CIBERER) (Grant 13-717/132.05 to RG), the “Instituto de Salud Carlos III” (FIS PI10/0703 and PI13/00556 to RG and PI15/00484 to MEG cofunded by FEDER), “Comunidad Autónoma de Madrid” (grant number S2010/BMD-2402 to R.G); T.G-M. receives grant support from the Universidad Autónoma de Madrid, FPI-UAM and F.Z-D. from the Ministerio de Educación, Cultura y Deporte, grant number FPU13/00544. M.E.G. is senior staff scientist at the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER).

Published
2016

20. Generation of a human iPSC line from a patient with an optic atrophy 'plus' phenotype due to a mutation in the OPA1 gene

Author

Rafael Garesse, Mario F. Fraga, Francisco Zurita-Díaz, Agustín F. Fernández, Ana Moreno-Izquierdo, Carmen Ayuso, M. Esther Gallardo, Teresa Galera-Monge, UAM. Departamento de Bioquímica, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red Enfermedades Raras (España), Ministerio de Educación, Cultura y Deporte (España), Instituto de Salud Carlos III, Comunidad de Madrid, and European Commission

Subjects
0301 basic medicine, Male, Optic atrophy 'plus' phenotyp, Medicina, DNA Mutational Analysis, Induced Pluripotent Stem Cells, Karyotype, Biology, OPA1 gene, Human iPSC line, GTP Phosphohydrolases, 03 medical and health sciences, Kruppel-Like Factor 4, stomatognathic system, Humans, lcsh:QH301-705.5, Gene, Cells, Cultured, Medicine(all), Genetics, Base Sequence, Cell Differentiation, Cell Biology, General Medicine, Fibroblasts, Cellular Reprogramming, Molecular biology, Phenotype, eye diseases, Optic Atrophy, 030104 developmental biology, lcsh:Biology (General), Microscopy, Fluorescence, embryonic structures, Mutation (genetic algorithm), Mutation, sense organs, Ipsc line, Developmental Biology, Transcription Factors
Abstract

Human iPSC line Oex2054SV.4 was generated from fibroblasts of a patient with an optic atrophy 'plus' phenotype associated with a heterozygous mutation in the OPA1 gene. Reprogramming factors OCT3/4, SOX2, CMYC and KLF4 were delivered using a non-integrative methodology that involves the use of Sendai virus., This work was supported by grants from the “Centro de Investigación Biomédica en Red en enfermedades raras” (CIBERER) (Grant 13-717/132.05 to RG), the “Instituto de Salud Carlos III” [Fondo de Investigación Sanitaria and European Regional Development Fund (ERDF/FEDER) funds PI10/0703 and PI13/00556 to RG and PI15/00484 to MEG], “Comunidad Autónoma de Madrid” (grant number S2010/BMD-2402 to R.G); T.G-M. receives grant support from the Universidad Autónoma de Madrid, FPI-UAM and F.Z-D from the Ministerio de Educación, Cultura y Deporte, grant number FPU13/00544. M.E.G. is staff scientist at the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER).

Published
2016

21. iPSCs, a future tool for therapeutic intervention in mitochondrial disorders: pros and cons

Author

Rafael Garesse, Teresa Galera, Francisco Zurita-Díaz, M. Esther Gallardo, Centro de Investigación Biomédica en Red Enfermedades Raras (España), Universidad Autónoma de Madrid, Ministerio de Educación, Cultura y Deporte (España), European Commission, Instituto de Salud Carlos III, and Comunidad de Madrid

Subjects
0301 basic medicine, Mitochondrial Diseases, DNA Copy Number Variations, Physiology, business.industry, Mitochondrial disease, Clinical Biochemistry, Induced Pluripotent Stem Cells, education, Psychological intervention, Cell Biology, Disease, Bioinformatics, medicine.disease, Regenerative medicine, Polymorphism, Single Nucleotide, 03 medical and health sciences, 030104 developmental biology, Intervention (counseling), Mutation, medicine, Humans, business, Induced pluripotent stem cell, health care economics and organizations
Abstract

Mitochondrial disorders, although individually are rare, taken together constitute a big group of diseases that share a defect in the oxidative phosphorylation system. Up to now, the development of therapies for these diseases is very slow and ineffective due in part to the lack of appropriate disease models. Therefore, there is an urgent need for the discovery of new therapeutic interventions. Regarding this, the generation of induced pluripotent stem cells (iPSCs) has opened new expectations in the regenerative medicine field. However, special cares and considerations must be taken into account previous to a replacement therapy., Contract grant sponsor: Centro de Investigacion Biomédica en Red en enfermedades raras (CIBERER); Contract grant number: 13-717/132.05. Contract grant sponsor: Instituto de Salud Carlos III cofunded by FEDER; Contract grant numbers: FIS PI10/0703, PI13/00556, PI15/00484. Contract grant sponsor: “Comunidad Autonoma de Madrid”; Contract grant number: S2010/BMD-2402. Contract grant sponsor: Universidad Autonoma de Madrid, Contract grant sponsor: Ministerio de Educacion, Cultura y Deporte; Contract grant number: FPU13/00544.

Published
2016

22. Generation of a human iPSC line from a patient with a mitochondrial encephalopathy due to mutations in the GFM1 gene

Author

Francisco Zurita-Díaz, Teresa Galera-Monge, Carmen Ayuso, Agustín F. Fernández, Ana Moreno-Izquierdo, M. Esther Gallardo, Rafael Garesse, Mario F. Fraga, UAM. Departamento de Bioquímica, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Ministerio de Educación, Cultura y Deporte (España), Universidad Autónoma de Madrid, European Commission, Comunidad de Madrid, Centro de Investigación Biomédica en Red Enfermedades Raras (España), and Instituto de Salud Carlos III

Subjects
0301 basic medicine, Medicina, Cellular differentiation, DNA Mutational Analysis, Induced Pluripotent Stem Cells, Karyotype, Transfection, Polymorphism, Single Nucleotide, Sendai virus, Cell Line, Mitochondrial Proteins, IPSC line, 03 medical and health sciences, Kruppel-Like Factor 4, Mitochondrial Encephalomyopathies, Humans, Induced pluripotent stem cell, Gene, Transcription factor, Genetics, Medicine(all), biology, Base Sequence, Cell Differentiation, General Medicine, Cell Biology, Fibroblasts, biology.organism_classification, Cellular Reprogramming, Peptide Elongation Factor G, 030104 developmental biology, Microscopy, Fluorescence, Mutations in the GFM1 gene, KLF4, Factor G1, embryonic structures, Cancer research, Female, Reprogramming, Developmental Biology, Plasmids, Transcription Factors, Mitochondrial encephalopathy
Abstract

Human iPSC line GFM1SV.25 was generated from fibroblasts of a child with a severe mitochondrial encephalopathy associated with mutations in the GFM1 gene, encoding the mitochondrial translation elongation factor G1. Reprogramming factors OCT3/4, SOX2, CMYC and KLF4 were delivered using a non integrative methodology that involves the use of Sendai virus., This work was supported by grants from the “Centro de Investigación Biomédica en Red en enfermedades raras” (CIBERER) (Grant 13-717/132.05 to RG), the “Instituto de Salud Carlos III” [Fondo de Investigación Sanitaria and Regional development fund (ERDF/FEDER) funds PI10/0703 and PI13/00556 to RG and PI15/00484 to MEG], “Comunidad Autónoma de Madrid” (Grant number S2010/BMD-2402 to RG); TG receives grant support from the Universidad Autónoma de Madrid (FPI-UAM) and FZD from the Ministerio de Educación, Cultura y Deporte (Grant FPU13/00544). MEG is staff scientist at the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER).

Published
2016

23. Generation of a human iPSC line from a patient with Leigh syndrome

Author

Rafael Garesse, Francisco Zurita, Ana Moreno-Izquierdo, M. Esther Gallardo, Teresa Galera, Cristina González-Páramos, Agustín F. Fernández, Mario F. Fraga, Universidad Autónoma de Madrid, Comunidad de Madrid, European Commission, Centro de Investigación Biomédica en Red Enfermedades Raras (España), Instituto de Salud Carlos III, UAM. Departamento de Bioquímica, and Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM)

Subjects
0301 basic medicine, Medicina, Cellular differentiation, Cell Culture Techniques, medicine.disease_cause, Cell Line, Kruppel-Like Factor 4, 03 medical and health sciences, MT-ND5, medicine, Humans, Leigh disease, Induced pluripotent stem cell, Medicine(all), Mutation, iPSC, biology, Cell Differentiation, Sequence Analysis, DNA, Cell Biology, General Medicine, IPS cells, biology.organism_classification, medicine.disease, Virology, Leigh syndrome, Sendai virus, Induced pluripotent stem cells, iPS cells, 030104 developmental biology, IPSC, KLF4, Karyotyping, embryonic structures, Leigh Disease, Reprogramming, Developmental Biology
Abstract

Human iPSC line LND554SV.3 was generated from heteroplasmic fibroblasts of a patient with Leigh syndrome carrying a mutation in the MT-ND5 gene (m.13513G. >. A; p.D393N). Reprogramming factors Oct3/4, Sox2, Klf4, and cMyc were delivered using a non-integrative methodology that involves the use of Sendai virus., This work was supported by grants from the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER) (grant 13-717/132.05 to RG), the “Instituto de Salud Carlos III” [Fondo de Investigación Sanitaria and Regional Development Fund (ERDF/FEDER) funds PI10/0703 and PI13/00556 to RG and PI15/00484 to MEG], “Comunidad Autónoma de Madrid” (grant number S2010/BMD-2402 to RG); TG receives grant support from the Universidad Autónoma de Madrid (FPI-UAM) and FZD from the Ministerio de Educación, Cultura y Deporte (FPU13/00544). MEG is a staff scientist at the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER).

Published
2016

24. Generation of a human iPSC line from a patient with a defect of intergenomic communication

Author

Rafael Garesse, Francisco Zurita, Ana Moreno-Izquierdo, Peter Schneiderat, M. Esther Gallardo, Cristina González-Páramos, Mario F. Fraga, Agustín F. Fernández, Teresa Galera, UAM. Departamento de Bioquímica, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), Instituto de Salud Carlos III, Universidad Autónoma de Madrid, Ministerio de Educación, Cultura y Deporte (España), and Centro de Investigación Biomédica en Red Enfermedades Raras (España)

Subjects
0301 basic medicine, Mitochondrial DNA, Medicina, Cellular differentiation, DNA Mutational Analysis, Induced Pluripotent Stem Cells, Karyotype, DNA-Directed DNA Polymerase, Transfection, medicine.disease_cause, Polymorphism, Single Nucleotide, Sendai virus, Cell Line, IPSC line, Kruppel-Like Factor 4, 03 medical and health sciences, medicine, Humans, Gene (POLG), Induced pluripotent stem cell, Gene, Polymerase, Medicine(all), Genetics, Mutation, Base Sequence, biology, Cell Differentiation, Cell Biology, General Medicine, Cellular Reprogramming, biology.organism_classification, DNA Polymerase gamma, p.Trp748Ser), 030104 developmental biology, Microscopy, Fluorescence, Mutation (c.2243GNC, embryonic structures, PG64SV.2, biology.protein, Female, Reprogramming, Plasmids, Transcription Factors, Developmental Biology
Abstract

Human iPSC line PG64SV.2 was generated from fibroblasts of a patient with a defect of intergenomic communication. This patient harbored a homozygous mutation (c.2243G>C; p.Trp748Ser) in the gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma gene (POLG). Reprogramming factors Oct3/4, Sox2, Klf4, and cMyc were delivered using a non integrative methodology that involves the use of Sendai virus., This work was supported by grants from the “Centro de Investigación Biomédica en Red en enfermedades raras” (CIBERER) (Grant 13-717/132.05 to RG), the “Instituto de Salud Carlos III” [Fondo de Investigación Sanitaria and Regional development fund (ERDF/FEDER) funds PI10/0703 and PI13/00556 to RG and PI15/00484 to MEG], “Comunidad Autónoma de Madrid” (Grant number S2010/BMD-2402 to RG); TG receives grant support from the Universidad Autónoma de Madrid (FPI-UAM) and FZD from the Ministerio de Educación, Cultura y Deporte (Grant FPU13/00544). MEG is staff scientist at the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER).

Published
2016

27. Reducing Internal Information Technology Resource Allocation Through Global Upstream Electronic Business Standards: A Case Study in Novozymes

Author

Douglas Steven Hill, Juan Francisco Zurita Duque, and Helle Skott

Subjects
Upstream (petroleum industry), Standards, Information Systems and Management, Process management, Electronic business, business.industry, Business process, Supply chain, Integration, Information technology, Benchmarking, Management Science and Operations Research, VMI, Management Information Systems, Vendor-managed inventory, Visibility, Operations management, business, Implementation, GUSI
Abstract

An increasing number of organisations are beginning to operate in a standardised business process environment suggesting that there is benefit in a standardised business messaging infrastructure.Novozymes A/S is the first known industrial biotech organisation in Denmark to apply the GS1 and the Consumer Goods Forum's global upstream standards initiative (GUSI) in a Vendor Managed Inventory (VMI) scenario. The combination of applying a standardised VMI business process using the aforementioned integration standards for electronic business messaging and pre-agreed standardised message choreography has been proven by Novozymes to add significant business benefit to their organisation.This case study methodology outlines the results of Novozymes' application of GUSI standards over three separate implementations replenishing 25 customers' factories and describes the resultant reduction in internal IT effort. The implementation data were collected from a total of twenty five factories (sites) which Novozymes, today, replenish using GUSI VMI. The 'ex post' results were then compared and interpreted against a Novozymes internal benchmarking analysis which was used an 'ex ante' base line.The findings strongly suggest that the GUSI VMI application provides not only reduced integration effort, but also is a foundational basis for higher rent generating processes and improved demand transparency management.

Published
2011
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